Next up in our series on What's New in E6 R3? Sponsor responsibilities for investigational product. There are some small changes here but with potentially big implications.
As in other sections, this one has been amended throughout to reference the possibility of using marketed products in an investigational trial. What was previously three sections has been collapsed into two. The following new details on blinded trials have been added:
- The sponsor should implement a blinding process that includes procedures to both prevent and detect "inappropriate" (i.e. accidental) unblinding.
- The mechanism for emergency unblinding should protect the identify of treatment assignments of other trial participants (previously, this was worded as "does not permit undetectable breaks of the blinding")
- Blinding should be protected where a participant's treatment assignment is unblinded for the purpose of safety reporting to regulatory authorities and/or IRB/IEC.
It is not clear whether the last step indicates that blinding of the study should not be compromised by safety report unblinding, or whether sponsors should take steps to restrict access to treatment assignment information for those participants who experience SUSARs. If the latter, we expect that the last step may cause some discussion. We have received feedback that some sponsors have moved away from distributing "dummy" expedited report submissions after they unblind SUSARs, thus effectively making study teams and investigators aware of treatment assignments for SUSARs (if a safety letter is not generated, then the participant who experienced a serious, unexpected event was not assigned to treatment).
Other changes are as follows:
- R3 now states that sponsors may supply trial participants with investigational product, assuming conformance with local regulations and favorable opinion from the IRB/IEC. Other responsibilities have been updated to take into account the possibility of direct distribution to participants.
- The sponsor's responsibility for ensuring that investigational products are stable has been amended to add that sponsors must make sure they are only used "within the current shelf-life"
- The step regarding retention of samples now states that where marketed products are used, sponsors do not need to keep samples as they are retained by the manufacturer
